Annulation of 2H-pyran onto 1-Oxa- or 1-azacyclohexane-2,4-diones and their analogues via sequential condensation with -substituted enals and 6π-electrocyclization

Article abstract of DOI:10.1246/bcsj.20130069

2H-Pyrans are constructed on a 1-oxa- or 1-azacyclohexane-2,4-dione core via Knoevenagel condensation with enals followed by 6π.electrocyclization, which are readily catalyzed with ethylenediammonium diacetate. This formal [3 + 3] strategy constitutes CO

Full text of DOI:10.1246/bcsj.20130069

870
Bull. Chem. Soc. Jpn. Vol. 86, No. 7, 870-879 (2013)
© 2013 The Chemical Society of Japan
Annulation of 2H-Pyran onto 1-Oxa- or 1-Azacyclohexane-2,4-diones
and Their Analogues via Sequential Condensation with
¡-Substituted Enals and 6³-Electrocyclization
Md. Imran Hossain,1 Elkhabiry Shaban,1 Taku Ikemi,1 Wei Peng,1
Hiroyuki Kawafuchi,2 and Tsutomu Inokuchi*1
1Division of Chemistry and Biotechnology, Graduate School of Natural Science and Technology,
Okayama University, 3-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530
2Toyama National College of Technology, Hongo-machi, Toyama 939-8630
Received March 8, 2013; E-mail: inokuchi@cc.okayama-u.ac.jp
2H-Pyrans are constructed on a 1-oxa- or 1-azacyclohexane-2,4-dione core via Knoevenagel condensation with enals
followed by 6³-electrocyclization, which are readily catalyzed with ethylenediammonium diacetate. This formal [3 + 3]
strategy constitutes C-O and C-C bond making and the diastereomer formation is circumvented using 6,6-disubstitution
with the same aryl group in the 1-oxacyclohexane-2,4-diones. This facile methodology significantly advances the access
to polysubstituted bicyclic 2H-pyrans with a versatile substrate choice and improved stability of the product.
Pyran rings including dihydro and tetrahydro analogues
connection with our interest in developing bicyclic pyrans as a
scaffold for biologically relevant compounds, like artemisinins
known as antimalarial agents,14 we examined the reactions of
cyclic substrates such as the 1-oxa- or 1-azacyclohexane-2,4-
diones II and enals I bearing an ¡-substituent R1 and compared
their reactivity to that of the acyclic 1,3-dicarbonyls. We also
attempted to optimize the conditions by choosing the amine
bases, solvents, and MW irradiation technique (Scheme 1).
are widely found as key structural motifs in various natural
products, and their biological significance has accordingly
stimulated synthetic activities.1 Among the known protocols
for the synthesis of 2H-pyran2 the electrocyclization of 2,4-
diene-2-ones is a highly straightforward method in terms of easy
C-O bond formations under thermal conditions, availability
of the starting materials with many choices of substituents,
and versatility of the resulting oxa-2,4-cyclohexenes for further
transformations.3 The iminium conditions are usually employed
for the preparation of 2,4-diene-2-one intermediates by the
reaction of 1,3-dicarbonyls with the conjugated 2-alkenals.4
However, this iminium-based strategy for the synthesis of
2H-pyrans has only been successful using 1,3-dicarbonyls of
highly enolizable structures, such as cyclohexane-1,3-diones,5
4-hydroxycoumarin,6 4-hydroxypyrones,7 and others8 as the
reactant. In addition to the iminium activation, acid-catalyzed
protocols with Lewis acids, such as InCl3,9 BF3¢Et2O, TiCl4,
Results and Discussion
To ensure the reaction of the cyclic ¢-keto ester and the
iminium of ¡-substituted enals, we employed compounds 2,
and examined the feasibility to produce the corresponding
bicyclic 2H-pyrans 3. The starting keto esters 2 were prepared
by the reaction of the substituted benzaldehydes 4 with the
dianion from 3-oxobutanoate generated either with LDA or
simply with K2CO3 by heating in ethanol (Scheme 2).15
The reactivity of 2 toward 1 was affected by the kind of
amine base and solvent used. Contrary to our previous study
on the reaction of acyclic ¢-keto esters with ¡-substituted
enals,12 attempts using secondary amines, such as piperidine,
pyrrolidine, diisopropylamine, and proline in THP or dichloro-
methane, resulted in a low yield of the target compound 3.
In place of these secondary amines, we tried to use primary
mono- and diamines for the iminium formation and the ensuing
condensation. Especially, ethylenediammonium diacetate (ED-
DA) has found potential uses as a catalyst in the reaction of 1,3-
dicarbonyls or their equivalents with various type of aldehydes
including enals, in acetonitrile,5 or ionic liquids,16 or under
solvent-free conditions.8
11
In(OTf)3,10 Brønsted acids,10 and I2 have been developed to
dictate the synthesis of the same 2H-pyran structures.
We previously reported the synthesis of 2,3,6-trisubstituted
2H-pyran-5-carboxylates from 2-substituted enals and acyclic
3-oxoalkanonates, in which we discussed the role of the C2
substituent of enals for the favorable formation of 2H-pyrans.12
Thus, the enals without an ¡-substituent led to the ensuing
Michael addition to the initially formed 2,4-diene-2-ones,
rather than electrocyclization.13 In the meantime, we found that
the obtained 2,3,6-trisubstituted 2H-pyran-5-carboxylates were
unstable during storage, and furthermore this protocol cannot
be applied to the reaction of 3-oxoalkanamides. Therefore, it
is worth addressing the following unsolved issues, i.e., whether
the substituent effect would arise in the sequential condensa-
tion of the cyclic structures of the keto ester, feasibility on keto
amides, and stability of the resulting bicyclic 2H-pyrans. In
Various conditions were tested for the reaction of 2f and
1f and the results are summarized in Table 1. As shown in
Entry 1, the condensation-6³-electrocyclization sequence was
achieved with the 2-aminoethanol-acetic acid mixture, though
Published on the web April 20, 2013; doi:10.1246/bcsj.20130069

M. I. Hossain et al.
Bull. Chem. Soc. Jpn. Vol. 86, No. 7 (2013)
871
O
O
4
R1
R2
3
10
9
X
X
5
8
6
CHO
2
Amine base
R2
+
O
O
7
R1
1
II
X = O, NR
I
III
R1, R2 = alkyl, aryl, etc.
Scheme 1. Annulation of 2H-pyran onto 1-oxa- or 1-azacyclohexane-2,4-diones with enals, forming the 1,6-dioxa- or 6-aza-1-
oxabicyclo[4.4.0]deca-3,9-dien-5-ones.
O
H
O
O
O
(i), (ii)
or (iii)
O
+
R3
R4
O
O
R3
R4
4a–i
2a–i
O
4
R1
R2
10
3
6
O
5
R3
R4
2
CHO
(iv)
R2
O
7
9
+
2a–i
8
1
R1
1a–h
3a–s
Compound 1: R1 = R2 = Me (1a); R1 = R2 = −(CH2)4− (1b); R1 = Me, R2 = 4-MeOC6H4 (1c); R1 = Me, R2 = Ph (1d);
R1 = Me, R2 = 4-BrC6H4 (1e); R1 = Me, R2 = 4-NO2C6H4 (1f); R1 = Me, R2 = 4-MeO2CC6H4 (1g);
R1 = Me, R2 = 4-ClC6H4 (1h)
Compound 2: R3 = H, R4 = Br (2a); R3 = Cl, R4 = H (2b); R3 = MeO, R4 = H (2c); R3 = H, R4 = F (2d); R3 = H, R4 = CF3 (2e);
R3 = H, R4 = Cl (2f); R3 = R4 = MeO (2g); R3 = H, R4 = MeO (2h); R3 = Br, R4 = H (2i)
Scheme 2. Synthesis of 1,6-dioxabicyclo[4.4.0]-3,9-diene-5-ones 3. Reagents and conditions: (i) LDA, THF, 0 °C, 1-3 h; (ii) HCl
(pH 1); (iii) K2CO3, EtOH, 45 °C, 16-18 h, HCl(aq); (iv) ethylenediammonium diacetate (EDDA) (5 mol %), MeOH, 2-3 h, 60 °C.
the yield of the desired 3m is low (15%). The formation of
3m is improved to 58% using the ethylenediamine-acetic acid
mixture in THP (Entry 2). Since these yields are moderate for
the desired 2H-pyran 3m irrespective of the solvents, such as
THP, THF, and CH2Cl2, at ambient temperature for 24 h, we
examined the effect of a protic solvent on this reaction. To our
delight, the addition of methanol to aprotic solvent CH2Cl2
improved the yield to 82% (Entry 5). In order to avoid the use
of the unpleasant solvent CH2Cl2, the reaction was conducted
in methanol (Entry 6), giving the desired 3m in good yield.
Finally, the desired 2H-pyran 3m was obtained in 80% yield
by adopting the conditions of heating at 60 °C in methanol
for the short reaction period of 2 h (Entry 7). This reaction
time was further decreased to a few minutes, by applying MW
irradiation at 60 °C,16 though the yield decreased to 64%
(Entry 8).
The effect of the kinds of substituents at the ¢-carbon
of ¡,¢-unsaturated aldehydes 1 on the reaction has also been
studied. The optimized conditions can be effectively used for
the reaction of 1 substituted with either an aliphatic or aromatic
group at the ¢-carbon. In Table 2, Entries 1-5, the yields of 1a
having an aliphatic substituent (R1 = R2 = CH3) are lower than
that obtained with cyclic aldehydes 1b (R1 = R2 = -(CH2)4-)
(Entry 6). No significant effect is observed for aromatic R2
bearing electron-withdrawing or -donating groups (Entries 7, 8,
and 11-19) compared to the aromatic R2 without such groups
(Entries 9 and 10).
In spite of the smooth formation of a 2,3-disubstituted 2H-
pyran onto the cyclic ¢-keto ester 2 by the condensation-
6³-cyclization sequence, the limitation of this method was
encountered in the reaction of 2f with cinnamaldehyde which
lacks an ¡-substituent. Thus, the reaction of 2f and cinnam-
aldehyde under the iminium conditions described above
resulted in a complicated product mixture.
We subsequently examined the scope of the reaction using
the optimized conditions (Entry 7, Table 1) for various aro-
matic ring-substituted cyclic keto esters 2 and ¡,¢-unsaturated
aldehydes 1. These results are summarized in Table 2.
Since the present condensation and cyclization sequence
invoked the installation of an R1 substituent at the C2 of the

872
Bull. Chem. Soc. Jpn. Vol. 86, No. 7 (2013)
Annulation of 2H-Pyran onto 1-Oxa- or 1-Azacyclohexane-2,4-diones
Table 1. Optimization of the Conditions for the Reaction of 2f and 1f Using Ethylenediammonium Diacetate (EDDA)a)
O
O
4
10
CH3
CHO
CH3
6
O
O
5
ammonium cat.
3
O
9 O
2
O2N
7
8
1
Cl
Cl
NO2
2f
1f
3m
Entry
Ammonium cat.b)
Solvent (10 mL)
Temp/°C
Time/h
Yieldc),d)/%
1
2
3
4
5
6
7
8e)
A
B
B
B
B
B
B
B
THP
THP
THF
CH2Cl2
CH2Cl2:MeOH = 1:1
MeOH
MeOH
rt.
rt.
rt.
rt.
rt.
rt.
60
60
24
24
24
24
24
24
2
2 min
15
58
45
40
82
78
80
64
MeOH
a) Reactions were carried out using 2f (1.0 mmol) and 1f (1.0 mmol) with ammonium catalyst at prescribed
temperature and for indicated time. b) A: 2-Hydroxyethylammonium acetate (5 mol %), B: ethylenedi-
ammonium diacetate (EDDA, 5 mol %). c) Yields based on chromatographically isolated products. d) All products
were a 1:1 mixture of diastereomers. e) A mixture of 2f (0.5 mmol) and 1f (0.5 mmol) in the presence of EDDA
(5 mol %) was irradiated with MW at 60 °C for 2 min.
tography. Therefore, we tried to eliminate the stereocenter at
the C6 of the ¤-lactone core 2 through attachment of the same
two substituents. Thus, the 6,6-disubstituted 1-oxacyclohexane-
2,4-dione 6 was prepared by the reaction of dianion from 3-
oxobutanoate and benzophenone (5) followed by an acidic
workup based on the method reported (Scheme 4).15
In a similar manner as described above, annulation of 2H-
pyran onto 1-oxacyclohexane-2,4-dione 6 was achieved by the
reaction with ¡-substituted enals 1 using ethylenediammonium
diacetate as a catalyst, giving the corresponding formal [3 + 3]
adducts 7a-7d in good yields (Table 3). This reaction was not
affected by two substituents at the C6 position of 6.
Figure 1. ORTEP drawing of crystal 3l.
Subsequently, we examined the annulations of the 2H-pyran
ring onto the N-protected 1-azacyclohexane-2,4-diones 10 by
enals 1, the reaction mechanism for formation of 3 can be
rationalized as described in Scheme 3. Thus, the Knoevenagel
condensation 1 and 2 would proceed via the iminium A,
affording the 2,4-dienones B and C, the stereochemical and
conformational isomers. Among them, (E)-C (s-cis), a requisite
configuration for the ensuing electrocyclization, would be
favored due to steric reasons. The equilibration between (Z)-B
and (E)-C would be catalyzed by the employed amine. Finally,
the s-cis conformer of (E)-C undergoes a spontaneous 6³-
electrocyclization to form the 2H-pyran 3.
To confirm the structure of the bicyclic 2H-pyran 3 formed
by this method, one of the isomers 3l, obtained by the reaction
of 1f and 2b, was subjected to X-ray crystallographic analysis
to determine its relative stereochemistry at C2 and C7. As
depicted in Figure 1, one of the isomers of 3l, isolated by
recrystallization, was unambiguously assigned as 2,7-trans
based on the X-ray analysis.
applying the above optimized conditions. In our preceding
paper,12 we encountered difficulty in the sequential condensa-
tion and 6³-electrocyclization with acyclic ¢-keto amides.
This was in sharp contrast to the smooth reaction using ¢-keto
esters, which could be ascribed to the electron-releasing nature
of the nitrogen atom of the amide.
The cyclic ¢-keto amides 10 were prepared by the Mannich
reaction of benzaldehydes 4 and malonic acid which was
followed by N-protection and the subsequent Claisen reaction
with Meldrum acid based on reported methods (Scheme 5).17
To our delight, the condensation-6³-electrocyclization
sequence on the cyclic amides 10 was achieved by the reac-
tion with ¡-substituted enals 1, affording the corresponding
11. Thus, the cyclic ¢-keto amides were more reactive than
the acyclic ones due to absence of intramolecular hydrogen
bonding in enol form. As shown in Table 4, Entries 1-4, this
reaction was not affected by the kind of substitution, electron-
withdrawing or -donating nature of aromatic group at the ¢-
carbon of 1. Unfortunately, this reaction sequence, affording
the 6-aza-1-oxabicyclo[4.4.0]deca-3,9-dien-5-ones 11, was not
stereoselective with respect to the substituents at C2 and C7.
To our disappointment, the reactions of the 5-substituted 2a-
2i with 3-aryl-2-alkenals 1 were not stereoselective, providing a
mixture of the 2,7-cis- and 2,7-trans isomers 3a-3s in an almost
1:1 ratio, which were hard to separate by usual flash chroma-

M. I. Hossain et al.
Bull. Chem. Soc. Jpn. Vol. 86, No. 7 (2013)
873
Table 2. Scope of the Reaction with Various 6-Aryl-1-oxacyclo-
hexane-2,4-diones 2 and ¡,¢-Unsaturated Aldehydes 1a)
Table 3. Scope of the Reaction of 6 with Various 3-Aryl-2-
methyl-2-enals 1a)
O
O
CHO
O
O
CHO
R2
R2
+
+
R3
R4
R1
O
O
R1
2a–i
2
6
1a, f–h
O
4
R1
R2
O
10
9
3
6
5
O
R1
R2
2
R3
R4
O
O
7
8
1
O
3a–s
Yieldb),c)
/%
Entry Compd R1 R2
R3
R4
7a–d
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
3o
3p
3q
3r
3s
Me Me
Me Me
Me Me
Me Me
Me Me
-(CH2)4-
Me 4-MeOC6H4
Me 4-MeOC6H4
Me Ph
H
Cl
H
Br
H
F
60
63
69
59
60
80
76
75
74
70
70
76
80
73
74
71
76
75
68
Entry
Compound
R1
R2
Yieldb)/%
1
2
3
4
7a
7b
7c
7d
Me
Me
Me
Me
4-NO2C6H4
4-MeOC6H4
4-ClC6H4
4-MeO2CC6H4
73
68
75
78
MeO MeO
H
H
H
H
CF3
CF3
Cl
a) Carried out by the reaction of keto esters (1.0 mmol) and
enals (1.0 mmol) with EDDA (5 mol %) in MeOH (10 mL) at
60 °C for 2 h. b) Isolated products.
CF3
MeO MeO
Me Ph
H
H
Cl
H
H
CF3
Cl
H
Cl
MeO
Me 4-BrC6H4
Me 4-NO2C6H4
Me 4-NO2C6H4
Me 4-NO2C6H4
Me 4-NO2C6H4
Me 4-NO2C6H4
Me 4-MeO2CC6H4
Me 4-ClC6H4
Me 4-ClC6H4
Table 4. Scope of the Reaction of 10 with Various 3-Aryl-2-
methyl-2-enals 1a)
Cl
MeO MeO
Br
H
H
H
H
CF3
CF3
Cl
CHO
+
R2
O
O
R1
N
O
a) Carried out by the reaction of keto esters (1.0 mmol) and
enals (1.0 mmol) with EDDA (5 mol %) in MeOH (10 mL) at
60 °C for 2 h. b) Isolated products. c) All products were a 1:1
mixture of diastereomers.
1a, c, d, f
O
10
O
O
Finally, we verified the scope of this reaction by applying
the optimized conditions to the condensation-6³-electrocycli-
zation of the benzopyridone derivative 12 with ¡-substituted
enals 1. The reaction smoothly proceeded under the above con-
ditions compared with the reported procedure that employed
the enals bearing no ¡-substitution (Table 5).
R1
R2
O
N
O
Cl
11a–d
R1
R2
Yieldb),c)/%
Conclusion
Entry
Compd
1
2
3
4
11a
11b
11c
11d
Me
Me
Me
Me
4-NO2C6H4
4-MeOC6H4
Ph
71
69
62
74
We developed a convergent access to the polysubstituted
1,6-dioxa- or 6-aza-1-oxabicyclo[4.4.0]deca-3,9-dien-5-ones
from 1-oxa- or 1-azacyclohexane-2,4-diones and ¡-substituted
enals. This protocol involves the tandem Knoevenagel con-
densation, which was readily catalyzed with ethylenediammo-
nium diacetate, and the subsequent 6³-electrocyclization. The
feasibility was dependent on the presence of a C2 substituent
on the enals. Cyclic 1,3-dicarbonyls were shown to be more
Me
a) Carried out by the reaction of keto amides (1.0 mmol) and
enals (1.0 mmol) with EDDA (5 mol %) in MeOH (10 mL) at
60 °C for 2 h. b) Isolated products. c) All products were a 1:1
mixture of diastereomers.

874
Bull. Chem. Soc. Jpn. Vol. 86, No. 7 (2013)
Annulation of 2H-Pyran onto 1-Oxa- or 1-Azacyclohexane-2,4-diones
O
O
H3N
-OAc
NH3
Ar
–
O
R1
R1
-OAc
2
H
N
R2
R2
+
NH3
CHO
–H2O
-OAc
H2N
-OAc
NH3
-OAc
1
A
R2
R1
O
O
O
R1
R2
O
R2
O
O
H
R1
Ar
O
Ar
O
Ar
O
(Z)-B
(E)-C (s-trans)
(E)-C (s-cis)
O
R1
O
6 -electrocyclization
Ar
O
R2
3
Scheme 3. Rationale for favorable formation of 3 by the condensation of 1 and 2 catalyzed by EDDA followed by
6³-electrocyclization.
O
O
O
(i), (ii)
O
O
+
O
O
5
6
Scheme 4. Synthesis of ¢-keto ¤-lactone 6. Reagents and conditions: (i) NaH, n-BuLi, THF, 0 °C; (ii) NaOH, THF, 0 °C.
Cl
HO
O
O
O
H
NH2
HN
O
O
O
(iii), (iv)
(ii)
COOH
(i)
N
O
Cl
O
Cl
4f
Cl
8
9
10
Scheme 5. Synthesis of N-protected ¢-keto amides 10: (i) malonic acid, ammonium acetate, EtOH, reflux, 5 h; (ii) (Boc)2O, dioxane/
water = 10/1, rt, overnight; (iii) meldrum acid, DMAP, DCC, DCM, 40 °C, overnight; (iv) ethyl acetate, reflux, 2 h.
reactive than acyclic ones, especially in the case of the amides.
Though the reaction of the C6 monosubstituted dicarbonyl
substrate with enals was non-stereoselective, this issue was
solved by substitution with the same group at the C6 position.
The resulting 2H-pyrans installed in the bicyclic system were
more stable than that in the monocyclic ones, and further
conversion of the resulting cyclized compounds into various
biologically relevant derivatives is our ongoing study.
Experimental
The commercially obtained reagents were used without
further purification. The 1H NMR, 13C NMR spectra were

M. I. Hossain et al.
Bull. Chem. Soc. Jpn. Vol. 86, No. 7 (2013)
875
Table 5. Scope of the Reaction of 12 with Various 3-Aryl-2-
methyl-2-enals 1a)
(s, 1H), 1.45 (d, J = 6.5 Hz) and 1.36 (d, J = 6.5 Hz) (total
3H); 13C NMR (151 MHz, CDCl3): ¤ 164.7, 162.5, 162.2,
137.4 (two peaks), 131.8 (two peaks), 128.1, 127.6 (two
peaks), 122.5, 112.4 (two peaks), 101.52, 101.1, 77.8 (two
peaks), 76.1, 75.7, 34.1, 33.9, 19.4 (two peaks), 18.8 (two
peaks). Anal. Calcd for C16H15BrO3: C, 57.33; H, 4.51%.
Found: C, 57.30; H, 4.38%.
OH
CHO
R2
+
R1
N
O
CH3
7-(3-Chlorophenyl)-2,3-dimethyl-7,8-dihydropyrano[4,3-
b]pyran-5(2H)-one (3b): Yield 63%; white solids; mp 101-
102 °C (from ethyl acetate-hexane); IR (KBr): ¯max = 3052,
2978, 2935, 2860, 1697, 1624, 1495, 1402, 1284, 1211,
1058 cm¹1; 1H NMR (400 MHz, CDCl3): ¤ 7.43 (d, J = 1.4 Hz,
1H), 7.38-7.20 (m, 3H), 6.12 (s) and 6.07 (s) (total 1H), 5.38
(t, J = 3.6 Hz) and 5.36 (t, J = 3.6 Hz) (total 1H), 4.93 (dq,
J = 13.1, 6.5 Hz, 1H), 2.78 (m, 1H), 2.58 (m, 1H), 1.75 (s, 2H),
1.59 (s, 1H), 1.45 (d, J = 6.5 Hz) and 1.37 (d, J = 6.5 Hz) (total
3H); 13C NMR (151 MHz, CDCl3): ¤ 164.9, 164.6, 162.5,
162.1, 140.3 (two peaks), 134.6, 129.9 (two peaks), 128.7,
128.1, 127.7, 126.1, 124.0 (two peaks), 112.3 (two peaks),
101.5, 101.1, 77.8 (two peaks), 75.9, 75.5, 34.0, 33.9, 19.4
(two peaks), 18.9 (two peaks). Anal. Calcd for C16H15ClO3: C,
66.10; H, 5.20%. Found: C, 66.28; H, 5.29%.
12
1d, f
R2
R1
O
N
O
CH3
13a–b
Entry
Compd
R1
R2
Yieldb)/%
1
2
13a
13b
Me
Me
4-NO2C6H6
Ph
95
92
a) Carried out by the reaction of 12 (1.0 mmol) and enals
(1.0 mmol) with EDDA (5 mol %) in MeOH (10 mL) at 60 °C
for 2 h. b) Isolated products.
7-(4-Fluorophenyl)-2,3-dimethyl-7,8-dihydropyrano[4,3-
b]pyran-5(2H)-one (3c): Yield 69%; white solids; mp 84-
85 °C (ethyl acetate-hexane); IR (KBr): ¯max = 3055, 2985,
¹1
2941, 1718, 1637, 1514, 1419, 1228, 1159, 1070 cm
;
measured on the Varian INOVA-600 or Varian INOVA-400
spectrometer, using CDCl3 as solvent and tetramethylsilane
(TMS) as internal standard. Melting points were determined
on a J-Science RFS-10 hot stage microscope. MW reaction
was performed with ¯ReactorEX, Shikoku Instrumentation
Co., Ltd., operated at 2.46 GHz.
Representative Procedure for the Synthesis of 7-(4-
Bromophenyl)-2,3-dimethyl-7,8-dihydropyrano[4,3-b]-
pyran-5(2H)-one (3a). To a solution of (E)-2-methylbut-2-
enal (1a, 84 mg, 1.0 mmol) in MeOH (10 mL), 2a (259 mg,
1.0 mmol) and ethylenediammonium diacetate (5 mol %) were
consecutively added. The reaction mixture was stirred at
60 °C for 2 h. After the reaction (checked by TLC), solvent
was concentrated under reduced pressure and water was added
to the residue. The crude products were extracted with ethyl
acetate, dried over MgSO4 and purified by flash column
chromatography.
Synthesis of 7-(4-Chlorophenyl)-3-methyl-2-(4-nitro-
phenyl)-7,8-dihydropyrano[4,3-b]pyran-5(2H)-one (3m) by
Microwave (MW) Irradiation. The solution of (E)-2-methyl-
3-(4-nitrophenyl)acrylaldehyde (1f, 95 mg, 0.5 mmol), 2b (112
mg, 0.5 mmol) and ethylenediammonium diacetate (5 mol %)
in MeOH (3 mL) was irradiated with MW at 60 °C for 2 min.
After the reaction (checked by TLC), it was worked up as
mentioned in the general method.
1H NMR (400 MHz, CDCl3): ¤ 7.45-7.32 (m, 2H), 7.15-7.00
(m, 2H), 6.12 (s) and 6.07 (s) (total 1H), 5.40 (t, J = 2.1 Hz)
and 5.37 (t, J = 2.1 Hz) (total 1H), 4.93 (dq, J = 13.1, 6.5 Hz,
1H), 2.80 (td, J = 17.2, 12.2 Hz, 1H), 2.55 (ddd, J = 17.4,
11.3, 4.1 Hz, 1H), 1.75 (s, 2H), 1.58 (s, 1H), 1.45 (d, J =
6.5 Hz) and 1.37 (d, J = 6.5 Hz) (total 3H); 13C NMR (151
MHz, CDCl3): ¤ 165.2, 164.8, 163.5, 162.7, 162.3, 161.8,
134.1, 128.0, 127.8 (two peaks), 127.6, 115.6 (two peaks),
112.4 (two peaks), 77.5 (two peaks), 76.2, 75.8, 34.2, 34.0,
19.4 (two peaks), 18.9 (two peaks). Anal. Calcd for C16H15FO3:
C, 70.06; H, 5.51%. Found: C, 69.98; H, 5.43%.
7-(3,4-Dimethoxyphenyl)-2,3-dimethyl-7,8-dihydro-
pyrano[4,3-b]pyran-5(2H)-one (3d):
solids; mp 137-138 °C (from ethyl acetate-hexane); IR (KBr):
max = 3055, 2974, 2918, 2839, 1674, 1627, 1516, 1422, 1261,
Yield 59%; white
¯
1159, 1026 cm¹1; H NMR (600 MHz, CDCl3): ¤ 6.97 (t, J =
2.2 Hz, 1H), 6.93-6.87 (m, 1H), 6.84 (dd, J = 8.2, 1.4 Hz, 1H),
6.12 (s) and 6.07 (s) (total 1H), 5.35 (ddd, J = 12.2, 6.0,
4.0 Hz, 1H), 4.92 (dd, J = 12.6, 6.3 Hz, 1H), 3.93-3.82 (d, J =
5.6 Hz, 6H), 2.84 (ddd, J = 25.2, 17.6, 12.3 Hz, 1H), 2.54 (td,
J = 17.3, 3.9 Hz, 1H), 1.75 (s, 3H), 1.44 (d, J = 6.5 Hz) and
1.37 (d, J = 6.5 Hz) (total 3H); 13C NMR (151 MHz, CDCl3):
¤ 165.5, 165.1, 162.9, 162.6, 149.1 (two peaks), 130.8 (two
peaks), 127.9, 127.5, 118.4 (two peaks), 112.5 (two peaks),
110.8 (two peaks), 109.2, 101.4, 101.0, 77.7 (two peaks), 76.4,
55.9 (two peaks), 34.2, 34.0, 19.3 (two peaks), 18.8 (two
peaks). Anal. Calcd for C18H20O5: C, 68.34; H, 6.37%. Found:
C, 68.45; H, 6.27%.
1
7-(4-Bromophenyl)-2,3-dimethyl-7,8-dihydropyrano[4,3-
b]pyran-5(2H)-one (3a): Yield 60%; white solids; mp 92-
93 °C (from ethyl acetate-hexane); IR (KBr): ¯max = 3053,
2982, 2929, 2856, 1697, 1622, 1489, 1402, 1296, 1217, 1066
2,3-Dimethyl-7-[4-(trifluoromethyl)phenyl]-7,8-dihydro-
¹1
cm
;
1H NMR (300 MHz, CDCl3): ¤ 7.59-7.48 (m, 2H),
pyrano[4,3-b]pyran-5(2H)-one (3e):
solids; mp 135-136 °C (from ethyl acetate-hexane); IR (KBr):
max = 3047, 2982, 2922, 2872, 1701, 1658, 1626, 1406, 1329,
Yield 60%; white
7.36-7.24 (m, 2H), 6.11 (s) and 6.06 (s) (total 1H), 5.43-5.31
(m, 1H), 4.93 (d, J = 6.5 Hz, 1H), 2.77 (dt, J = 17.8, 11.8 Hz,
1H), 2.56 (ddd, J = 17.5, 6.7, 4.2 Hz, 1H), 1.75 (s, 2H), 1.58
¯
1
1229, 1066 cm¹1; H NMR (400 MHz, CDCl3): ¤ 7.66 (d, J =

876
Bull. Chem. Soc. Jpn. Vol. 86, No. 7 (2013)
Annulation of 2H-Pyran onto 1-Oxa- or 1-Azacyclohexane-2,4-diones
8.3 Hz, 2H), 7.55 (d, J = 8.1 Hz, 2H), 6.10 (d, J = 19.4 Hz,
1H), 5.47 (dt, J = 11.8, 4.1 Hz, 1H), 4.94 (p, J = 5.1 Hz, 1H),
2.86-2.70 (m, 1H), 2.62 (ddd, J = 17.4, 8.5, 4.2 Hz, 1H), 1.75
(s, 2H), 1.62 (s, 1H), 1.46 (d, J = 6.5 Hz) and 1.37 (d, J =
6.5 Hz) (total 3H); 13C NMR (151 MHz, CDCl3): ¤ 164.8,
164.5, 162.4, 162.0, 142.3 (two peaks), 130.8, 130.6, 128.2,
127.8, 126.1, 125.98-125.38 (multiple peaks), 112.33 (two
peaks), 101.5, 77.9 (two peaks), 75.9, 75.5, 34.1, 33.9, 19.4
(two peaks), 18.9 (two peaks). Anal. Calcd for C17H15F3O3: C,
62.96; H, 4.66%. Found: C, 62.87; H, 4.71%.
75.4, 55.3 (two peaks), 33.8 (two peaks), 19.39. Anal. Calcd
for C23H19F3O4: C, 66.34; H, 4.60%. Found: C, 63.15; H,
4.37%.
7-(3,4-Dimethoxyphenyl)-3-methyl-2-phenyl-7,8-dihydro-
pyrano[4,3-b]pyran-5(2H)-one (3i):
solids; mp 90-91 °C (from ethyl acetate-hexane); IR (KBr):
max = 3068, 2984, 2937, 2837, 1705, 1624, 1516, 1400, 1263,
Yield 80%; white
¯
¹1
1159, 1026 cm
;
1H NMR (600 MHz, CDCl3): ¤ 7.53-7.30
(m, 5H), 7.05-6.75 (m, 3H), 6.38 (d, J = 37.3 Hz, 1H), 5.74
(d, J = 10.9 Hz, 1H), 5.37 (dd, J = 11.9, 4.0 Hz) and 5.28 (dd,
J = 12.2, 3.9 Hz) (total 1H), 3.87 (dd, J = 13.8, 8.0 Hz, 6H),
2.86 (dd, J = 17.4, 12.2 Hz), 2.72 (dd, J = 17.8, 11.9 Hz), 2.55
(dd, J = 17.9, 4.1 Hz), and 2.44 (dd, J = 17.5, 3.9 Hz) (total
2H), 1.63 (d, J = 4.4 Hz, 3H); 13C NMR (151 MHz, CDCl3):
¤ 165.5, 165.5, 162.4, 149.1 (two peaks), 137.8, 133.5, 130.5,
130.1, 129.42 (two peaks), 128.9 (two peaks), 128.4, 128.0,
127.8, 125.6, 125.2, 118.5, 118.3, 113.6, 110.8 (two peaks),
109.2 (two peaks), 101.1, 83.3, 83.2, 76.3, 55.9-55.7 (multiple
peaks), 33.9 (two peaks), 31.5, 22.6, 19.37 (two peaks), 14.1.
Anal. Calcd for C23H22O5: C, 73.00; H, 5.86%. Found: C,
72.86; H, 5.85%.
3-[4-(Trifluoromethyl)phenyl]-3,4,6,7,8,9-hexahydro-
pyrano[4,3-b]chromen-1(5aH)-one (3f): Yield 73%; white
solids; mp 201-202 °C (from ethyl acetate-hexane); IR (KBr):
¯
max = 3056, 2951, 2939, 2864, 1699, 1622, 1413, 1337, 1163,
1064 cm¹1; 1H NMR (400 MHz, CDCl3): ¤ 7.65 (d, J = 8.3 Hz,
2H), 7.53 (d, J = 8.5 Hz, 2H), 6.01-5.94 (m, 1H), 5.45 (dd,
J = 12.0, 4.1 Hz, 1H), 5.05 (ddd, J = 16.8, 11.4, 5.2 Hz, 1H),
2.81-2.68 (m, 1H), 2.63-2.49 (m, 1H), 2.40 (dd, J = 14.1,
1.9 Hz, 1H), 2.20-2.03 (m, 1H), 2.03-1.86 (m, 2H), 1.85-
1.61 (m, 2H), 1.54-1.23 (m, 2H); 13C NMR (101 MHz, CDCl3):
¤ 164.8 (two peaks), 163.4 (two peaks), 142.3, 131.5 (two
peaks), 126.1 (two peaks), 125.6 (four peaks), 125.2, 122.5,
109.2, 108.9, 99.6, 99.3, 80.5, 80.3, 75.6 (two peaks), 35.0
(two peaks), 34.0, 33.0, 32.8, 26.8 (two peaks), 24.5 (two
peaks). Anal. Calcd for C19H17F3O3: C, 65.14; H, 4.89%.
Found: C, 65.11; H, 4.67%.
3-Methyl-2-phenyl-7-[4-(trifluoromethyl)phenyl]-7,8-di-
hydropyrano[4,3-b]pyran-5(2H)-one (3j): Yield 80%; white
solids; mp 137-138 °C (from ethyl acetate-hexane); IR (KBr):
¯
max = 3064, 3028, 2914, 1707, 1665, 1626, 1402, 1337, 1159,
1062 cm¹1; 1H NMR (300 MHz, CDCl3): ¤ 7.69-7.55 (m, 2H),
7.55-7.40 (m, 5H), 7.40-7.29 (m, 2H), 6.41 (s) and 6.35 (s)
(total 1H), 5.75 (d, J = 8.3 Hz, 1H), 5.50 (t, J = 7.8 Hz) and
5.41 (dd, J = 12.0, 4.1 Hz) (total 1H), 2.80 (dd, J = 17.5, 11.9
Hz), 2.66 (d, J = 7.7 Hz), and 2.52 (dd, J = 17.5, 4.2 Hz) (total
2H), 1.64 (d, J = 15.9 Hz, 3H); 13C NMR (101 MHz, CDCl3):
¤ 164.7, 162.1, 161.8, 142.0, 137.6 (two peaks), 129.5 (two
peaks), 129.0 (two peaks), 128.0, 127.8, 126.3-125.6 (multiple
peaks), 125.6 (two peaks), 113.4 (two peaks), 101.3, 83.4, 83.2,
75.4, 33.8 (two peaks), 19.3. Anal. Calcd for C22H17F3O3: C,
68.39; H, 4.43%. Found: C, 68.44; H, 4.50%.
7-(4-Chlorophenyl)-2-(4-methoxyphenyl)-3-methyl-7,8-
dihydropyrano[4,3-b]pyran-5(2H)-one (3g):
Yield 72%;
white solids; mp 122-123 °C (from ethyl acetate-hexane); IR
(KBr): ¯max = 3003, 2941, 2908, 2839, 1703, 1629, 1512,
1
1400, 1253, 1159, 1064 cm¹1; H NMR (600 MHz, CDCl3): ¤
7.39-7.24 (m, 6H), 6.94 (d, J = 8.7 Hz, 1H), 6.88 (d, J =
8.7 Hz, 1H), 6.41 (s) and 6.34 (s) (total 1H), 5.70 (d, J =
16.5 Hz, 1H), 5.40 (dd, J = 10.6, 5.0 Hz) and 5.30 (dd, J =
12.0, 4.0 Hz) (total 1H), 3.83 (d, J = 11.7 Hz, 3H), 2.78 (dd,
J = 17.5, 12.0 Hz), 2.66-2.54 (m), and 2.44 (dd, J = 17.5,
4.0 Hz) (total 2H), 1.63 (d, J = 3.9 Hz, 3H); 13C NMR (151
MHz, CDCl3): ¤ 165.0, 162.3, 161.9, 160.4 (two peaks), 136.8,
136.7, 134.3 (two peaks), 129.7 (two peaks), 129.5, 129.3,
128.8 (two peaks), 127.3 (two peaks), 125.9, 125.5, 114.2
(two peaks), 113.5 (two peaks), 101.2, 100.6, 82.9, 82.8,
75.9, 75.6, 55.3 (two peaks), 33.8 (two peaks), 19.3. Anal.
Calcd for C22H19ClO4: C, 69.02; H, 5.00%. Found: C, 69.12;
H, 5.08%.
2-(4-Bromophenyl)-7-(4-chlorophenyl)-3-methyl-7,8-di-
hydropyrano[4,3-b]pyran-5(2H)-one (3k):
Yield 71%;
white solids; mp 80-81 °C (from ethyl acetate-hexane); IR
(KBr): ¯ = 3065, 2972, 2912, 2853, 1699, 1624, 1491, 1398,
1294, 1155, 1070 cm¹1; 1H NMR (600 MHz, CDCl3): ¤ 7.57 (d,
J = 8.4 Hz, 1H), 7.51 (d, J = 8.4 Hz, 1H), 7.43-7.19 (m, 6H),
6.39 (d, J = 37.8 Hz, 1H), 5.70 (d, J = 16.0 Hz, 1H), 5.40 (dd,
J = 10.9, 4.8 Hz) and 5.31 (dd, J = 12.0, 4.0 Hz) (total 1H),
2.79 (dd, J = 17.4, 11.9 Hz), 2.61 (dd, J = 13.2, 7.9 Hz), and
2.45 (dd, J = 17.5, 4.0 Hz) (total 2H), 1.63 (d, J = 4.1 Hz,
3H); 13C NMR (151 MHz, CDCl3): ¤ 161.8, 136.6, 136.5,
134.4, 132.2 (two peaks), 131.8, 131.6, 129.7, 129.6, 128.8
(two peaks), 127.3 (two peaks), 124.9, 123.7, 113.9 (two
peaks), 100.9, 82.4, 82.2, 76.0, 75.6, 33.7, 19.3. Anal. Calcd
for C21H16BrClO3: C, 58.42; H, 3.74%. Found: C, 58.98; H,
3.48%.
2-(4-Methoxyphenyl)-3-methyl-7-[4-(trifluoromethyl)-
phenyl]-7,8-dihydropyrano[4,3-b]pyran-5(2H)-one
(3h):
Yield 75%; yellowish solids; mp 63-64 °C (from ethyl
acetate-hexane); IR (KBr): ¯max = 3059, 2937, 2841, 1708,
1622, 1512, 1402, 1327, 1251, 1170, 1066 cm¹1; 1H NMR (400
MHz, CDCl3): ¤ 7.62 (dd, J = 11.7, 8.5 Hz, 2H), 7.49 (dd, J =
12.0, 8.2 Hz, 2H), 7.40-7.32 (m, 1H), 7.32-7.21 (m, 1H),
7.00-6.91 (m, 1H), 6.91-6.84 (m, 1H), 6.41 (s) and 6.35 (s)
(total 1H), 5.71 (d, J = 10.9 Hz, 1H), 5.53-5.44 (m) and 5.39
(dd, J = 11.9, 4.0 Hz) (total 1H), 3.80 (d, J = 12.8 Hz, 3H),
2.78 (dd, J = 17.4, 11.9 Hz), 2.64 (d, J = 7.2 Hz), and 2.50
(dd, J = 17.4, 4.1 Hz) (total 2H), 1.64 (s, 3H); 13C NMR
(101 MHz, CDCl3): ¤ 164.7, 162.1, 161.8, 160.4, 142.2, 129.5
(three peaks), 126.19, 126.2, 125.8 (two peaks), 114.30 (two
peaks), 113.44 (two peaks), 101.33, 82.9 (two peaks), 75.8,
7-(3-Chlorophenyl)-3-methyl-2-(4-nitrophenyl)-7,8-di-
hydropyrano[4,3-b]pyran-5(2H)-one (3l): Yield 76%; white
solids; mp 150-151 °C (from ethyl acetate-hexane); IR (KBr):
¯ = 3066, 2941, 2918, 2850, 1712, 1631, 1518, 1337, 1398,
1
1350, 1155, 1058 cm¹1; H NMR (400 MHz, CDCl3): ¤ 8.34-
8.26 (m, 1H), 8.26-8.18 (m, 1H), 7.67-7.59 (m, 1H), 7.56-7.48
(m, 1H), 7.44-7.17 (m, 4H), 6.47 (s) and 6.41 (d, J = 0.6 Hz)

M. I. Hossain et al.
Bull. Chem. Soc. Jpn. Vol. 86, No. 7 (2013)
877
(total 1H), 5.83 (d, J = 15.2 Hz, 1H), 5.42 (t, J = 7.7 Hz), and
5.32 (dd, J = 12.0, 4.0 Hz) (total 1H), 2.83 (dd, J = 17.6, 12.0
Hz), 2.66 (d, J = 7.6 Hz), and 2.50 (dd, J = 17.6, 4.1 Hz) (total
2H), 1.65 (dd, J = 14.3, 8.8 Hz, 3H); 13C NMR (101 MHz,
CDCl3): ¤ 164.3, 164.1, 161.9, 161.5, 148.4, 144.1 (two peaks),
139.9 (two peaks), 134.6 (two peaks), 129.9 (two peaks),
128.82 (two peaks), 126.8 (two peaks), 124.7, 124.4-123.9
(multiple peaks), 123.9 (two peaks), 114.5 (two peaks), 101.7,
101.1, 81.7, 81.4, 75.6 (two peaks), 75.5, 33.6 (two peaks),
19.3. Anal. Calcd for C21H16ClNO5: C, 63.40; H, 4.05; N,
3.52%. Found: C, 63.41; H, 4.09; N, 3.47%.
Crystallographic data have been deposited with The
Cambridge Crystallographic Data Centre: Deposition number
CCDC-931766 for compound 3l. Copies of the data can be
obtained free of charge via www.ccdc.cam.ac.uk/data_request/
cif (or from The Cambridge Crystallographic Data Centre, 12,
Union Road, Cambridge, CB2 1EZ, UK; e-mail: data_request@
ccdc.cam.ac.uk).
(m, 1H), 7.58-7.51 (m, 1H), 6.92 (dd, J = 3.6, 1.9 Hz, 1H),
6.90-6.75 (m, 2H), 6.47 (s) and 6.41 (s) (total 1H), 5.83 (d,
J = 11.2 Hz, 1H), 5.39 (dd, J = 11.4, 4.2 Hz) and 5.29 (dd,
J = 12.1, 3.9 Hz) (total 1H), 3.86 (t, J = 2.8 Hz, 6H), 2.89 (dd,
J = 17.6, 12.1 Hz), 2.72 (dd, J = 17.9, 11.4 Hz), 2.59 (dd,
J = 17.9, 4.3 Hz), and 2.45 (dd, J = 17.6, 4.0 Hz) (total 2H),
1.65 (d, J = 3.7 Hz, 3H); 13C NMR (101 MHz, CDCl3): ¤
164.9, 164.6, 162.3, 161.9, 149.1 (two peaks), 148.4, 144.3
(two peaks), 130.3 (two peaks), 128.8 (two peaks), 124.5,
124.2 (two peaks), 118.3, 114.6, 110.7 (two peaks), 109.1 (two
peaks), 101.59, 101.1, 81.5 (two peaks), 76.3, 55.8 (two peaks),
33.7 (two peaks), 19.2. Anal. Calcd for C23H21NO7: C, 65.24;
H, 5.00; N, 3.31%. Found: C, 65.23; H, 4.83; N, 3.22%.
7-(3-Bromophenyl)-3-methyl-2-(4-nitrophenyl)-7,8-di-
hydropyrano[4,3-b]pyran-5(2H)-one (3p):
Yield 71%;
white solid; mp 160-161 °C (from ethyl acetate-hexane); IR
(KBr): ¯ = 3082, 2956, 2916, 2844, 1707, 1629, 1521, 1396,
¹1
1384, 1286, 1155, 1058 cm
;
1H NMR (400 MHz, CDCl3):
7-(4-Chlorophenyl)-3-methyl-2-(4-nitrophenyl)-7,8-di-
¤ 8.33-8.26 (m, 1H), 8.26-8.19 (m, 1H), 7.66-7.59 (m, 1H),
7.56-7.49 (m, 2H), 7.49-7.42 (m, 1H), 7.33-7.17 (m, 2H), 6.47
(s) and 6.41 (d, J = 0.6 Hz) (total 1H), 5.83 (d, J = 15.2 Hz,
1H), 5.46-5.37 (m) and 5.32 (dd, J = 12.0, 4.0 Hz) (total 1H),
2.83 (dd, J = 17.6, 12.0 Hz), 2.65 (d, J = 7.6 Hz), and 2.49
(dd, J = 17.6, 4.1 Hz) (total 2H), 1.65 (dd, J = 13.4, 8.0 Hz,
3H); 13C NMR (101 MHz, CDCl3): ¤ 164.3, 164.1, 161.9,
161.5, 148.4, 144.1 (two peaks), 140.1 (two peaks), 131.7 (two
peaks), 130.2 (two peaks), 128.96 (two peaks), 128.7, 124.7,
124.3 (two peaks), 122.7, 114.5 (two peaks), 101.7, 101.1,
81.7, 81.4, 75.7, 75.4, 33.6 (two peaks), 19.3. Anal. Calcd for
C21H16BrNO5: C, 57.03; H, 3.65; N, 3.17%. Found: C, 57.05;
H, 3.43; N, 3.51%.
Methyl 4-{3-Methyl-5-oxo-7-[4-(trifluoromethyl)phenyl]-
2,5,7,8-tetrahydropyrano[4,3-b]pyran-2-yl}benzoate (3q):
Yield 76%; white solids; mp 158-159 °C (from ethyl acetate-
hexane); IR (KBr): ¯ = 3061, 2955, 2914, 1708, 1633, 1398,
1284, 1166 cm¹1; 1H NMR (600 MHz, CDCl3): ¤ 8.13-8.08 (m,
1H), 8.06-8.01 (m, 1H), 7.62 (dd, J = 19.1, 8.2 Hz, 2H), 7.55-
7.45 (m, 3H), 7.44-7.39 (m, 1H), 6.44 (s) and 6.38 (s) (total
1H), 5.79 (d, J = 17.1 Hz, 1H), 5.51 (dd, J = 9.1, 6.4 Hz) and
5.41 (dd, J = 11.9, 4.1 Hz) (total 1H), 3.94 (d, J = 11.1 Hz,
3H), 2.86-2.77 (m), 2.69-2.63 (m), and 2.52 (dd, J = 17.5,
4.1 Hz) (total 2H), 1.64 (d, J = 7.0 Hz, 3H); 13C NMR (151
MHz, CDCl3): ¤ 166.4 (two peaks), 164.5, 164.2, 161.9, 161.6,
142.1 (two peaks), 131.2 (two peaks), 130.3 (two peaks),
127.9, 127.7, 126.1 (two peaks), 126.0-125.3 (multiple peaks),
125.0, 113.9 (two peaks), 101.5, 82.6, 82.4, 75.8, 75.4, 52.3
(two peaks), 33.7 (two peaks), 19.3 (two peaks). Anal. Calcd
for C24H19F3O5: C, 64.86; H, 4.31%. Found: C, 64.68; H,
4.27%.
hydropyrano[4,3-b]pyran-5(2H)-one (3m):
Yield 80%;
white solids; mp 163-164 °C (from ethyl acetate-hexane); IR
(KBr): ¯ = 3072, 2970, 2924, 2853, 1714, 1622, 1519, 1392,
1
1364, 1286, 1151, 1057 cm¹1; H NMR (400 MHz, CDCl3): ¤
8.33-8.18 (m, 2H), 7.63 (d, J = 8.7 Hz, 1H), 7.58-7.50 (m,
1H), 7.41-7.21 (m, 4H), 6.46 (s) and 6.40 (s) (total 1H), 5.83
(d, J = 12.3 Hz, 1H), 5.42 (dd, J = 10.3, 5.4 Hz) and 5.33
(dd, J = 11.9, 4.0 Hz) (total 1H), 2.83 (dd, J = 17.6, 11.9 Hz),
2.64 (t, J = 7.0 Hz), and 2.48 (dd, J = 17.6, 4.0 Hz) (total
2H), 1.64 (t, J = 7.4 Hz, 3H); 13C NMR (101 MHz, CDCl3):
¤ 164.5, 164.2, 161.9, 161.6, 148.4, 144.2 (two peaks), 136.4
(two peaks), 134.5, 128.8 (two peaks), 127.27, 124.74, 124.4-
124.0 (multiple peaks), 114.5 (two peaks), 101.6, 101.1, 81.7,
81.5, 76.0, 75.6, 33.7 (two peaks), 19.3. Anal. Calcd for
C21H16ClNO5: C, 63.40; H, 4.05; N, 3.52%. Found: C, 63.41;
H, 3.90; N, 3.46%.
7-(4-Methoxyphenyl)-3-methyl-2-(4-nitrophenyl)-7,8-di-
hydropyrano[4,3-b]pyran-5(2H)-one (3n):
Yield 73%;
white solids; mp 150-151 °C (from ethyl acetate-hexane); IR
(KBr): ¯max = 3055, 2933, 2908, 2839, 1708, 1628, 1523,
¹1
1394, 1350, 1244, 1153, 1057 cm
.
1H NMR (400 MHz,
CDCl3): ¤ 8.33-8.26 (m, 1H), 8.26-8.19 (m, 1H), 7.66-7.59
(m, 1H), 7.57-7.50 (m, 1H), 7.32-7.21 (m, 2H), 6.92-6.81 (m,
2H), 6.47 (s) and 6.41 (s) (total 1H), 5.82 (d, J = 14.1 Hz, 1H),
5.40 (dd, J = 11.1, 4.4 Hz) and 5.29 (dd, J = 12.0, 4.0 Hz)
(total 1H), 3.79 (d, J = 0.5 Hz, 3H), 2.88 (dd, J = 17.6,
12.0 Hz), 2.76-2.55 (m), and 2.44 (dd, J = 17.6, 4.0 Hz) (total
2H), 1.65 (d, J = 3.9 Hz, 3H); 13C NMR (101 MHz, CDCl3):
¤ 164.9, 164.6, 162.3, 161.9, 159.8, 148.4, 144.3 (two peaks),
129.9 (two peaks), 128.8 (two peaks), 127.4 (two peaks),
124.5, 124.1 (three peaks), 114.6 (two peaks), 113.9 (two
peaks), 101.6, 101.1, 81.6, 81.4, 76.2, 55.2, 33.6, 19.2. Anal.
Calcd for C22H19NO6: C, 67.17; H, 4.87; N, 3.56%. Found:
C, 67.30; H, 4.71; N, 3.50%.
2-(4-Chlorophenyl)-3-methyl-7-[4-(trifluoromethyl)phen-
yl]-7,8-dihydropyrano[4,3-b]pyran-5(2H)-one (3r): Yield
75%; white solids; mp 75-76 °C (from ethyl acetate-hexane);
IR (KBr): ¯ = 3057, 2926, 2874, 1699, 1627, 1508, 1400,
1
7-(3,4-Dimethoxyphenyl)-3-methyl-2-(4-nitrophenyl)-7,8-
1329, 1292, 1166 cm¹1; H NMR (600 MHz, CDCl3): ¤ 7.63
dihydropyrano[4,3-b]pyran-5(2H)-one (3o):
white solids; mp 152-153 °C (from ethyl acetate-hexane);
Yield 74%;
(dd, J = 15.2, 8.3 Hz, 2H), 7.53-7.45 (m, 2H), 7.41 (s, 1H),
7.39 (s, 1H), 7.35 (d, J = 8.5 Hz, 1H), 7.29 (d, J = 8.5 Hz, 1H),
6.43 (s) and 6.37 (s) (total 1H), 5.72 (d, J = 16.2 Hz, 1H), 5.49
(t, J = 7.8 Hz) and 5.40 (dd, J = 11.9, 4.0 Hz) (total 1H), 2.80
(dd, J = 17.5, 11.9 Hz), 2.64 (d, J = 7.7 Hz), and 2.50 (dd, J =
IR (KBr): ¯max = 3072, 2937, 2914, 2839, 1701, 1633, 1521,
¹1
1398, 1341, 1259, 1157, 1058 cm
.
1H NMR (400 MHz,
CDCl3): ¤ 8.32-8.26 (m, 1H), 8.26-8.19 (m, 1H), 7.67-7.60

878
Bull. Chem. Soc. Jpn. Vol. 86, No. 7 (2013)
Annulation of 2H-Pyran onto 1-Oxa- or 1-Azacyclohexane-2,4-diones
17.5, 4.1 Hz) (total 2H), 1.64 (d, J = 5.2 Hz, 3H); 13C NMR
(151 MHz, CDCl3): ¤ 164.6, 164.1, 161.6, 142.1, 141.9, 135.9
(two peaks), 135.5 (two peaks), 129.3 (two peaks), 126.1
(two peaks), 125.9-125.4 (multiple peaks), 125.1, 113.9 (two
peaks), 101.5, 100.9, 82.4, 82.2, 75.8, 75.4, 33.8 (two peaks),
31.5, 22.6, 19.3, 14.2. Anal. Calcd for C22H16ClF3O3: C, 62.79;
H, 3.83%. Found: C, 62.62; H, 3.58%.
for C27H21ClO3: C, 75.61; H, 4.94%. Found: C, 75.43; H,
5.19%.
Methyl 4-(3-Methyl-5-oxo-7,7-diphenyl-2,5,7,8-tetra-
hydropyrano[4,3-b]pyran-2-yl)benzoate (7d): Yield 72%;
white solids; mp 174-175 °C (from ethyl acetate-hexane); IR
(KBr): ¯ = 3061, 2999, 2910, 1705, 1633, 1400, 1286, 1197
1
cm¹1; H NMR (600 MHz, CDCl3): ¤ 8.00-7.95 (m, 2H), 7.36
3,6-Bis(4-chlorophenyl)-7-methyl-3,4,5,6-tetrahydro-1H-
isochromen-1-one (3s): Yield 68%; white solids; mp 131-
132 °C (from ethyl acetate-hexane); IR (KBr): ¯ = 3068, 2931,
2910, 1608, 1489, 1398, 1296, 1157 cm¹1; 1H NMR (600 MHz,
CDCl3): ¤ 7.44-7.23 (m, 8H), 6.42 (s) and 6.36 (s) (total 1H),
5.71 (d, J = 16.2 Hz, 1H), 5.40 (dd, J = 10.8, 4.8 Hz) and 5.31
(dd, J = 11.9, 4.0 Hz) (total 1H), 2.79 (dd, J = 17.5, 12.0 Hz),
2.68-2.53 (m), 2.45 (dd, J = 17.5, 4.0 Hz) (total 2H), 1.63 (d,
J = 4.5 Hz, 3H); 13C NMR (151 MHz, CDCl3): ¤ 164.8, 164.5,
162.1, 161.7, 136.6, 136.5, 136.0 (two peaks), 135.4 (two
peaks), 134.4, 129.4, 129.3-129.1 (multiple peaks), 128.8 (two
peaks), 127.3 (two peaks), 125.4, 125.0, 113.9 (two peaks),
101.4, 100.9, 82.3, 82.2, 76.0, 75.6, 33.8, 19.3. Anal. Calcd for
C21H16Cl2O3: C, 65.13; H, 4.16%. Found: C, 65.46; H, 4.92%.
The compounds 7a-7d, 11a-11d, 13a, and 13b were
prepared in the same manner as described for 3a.
(dd, J = 8.3, 1.1 Hz, 2H), 7.34-7.16 (m, 10H), 6.26 (s, 1H),
5.71 (s, 1H), 3.95 (s, 3H), 3.27 (d, J = 17.5 Hz, 1H), 3.15 (d,
J = 17.5 Hz, 1H), 1.55 (s, 3H); 13C NMR (151 MHz, CDCl3):
¤ 166.5, 164.3, 161.8, 143.1, 142.5, 142.3, 130.9, 130.1, 128.4
(two peaks), 127.9-127.7 (multiple peaks), 125.7, 125.43,
124.4, 113.6, 102.1, 84.0, 82.5, 52.3, 37.2, 19.1. Anal. Calcd
for C29H24O5: C, 76.98; H, 5.35%. Found: C, 76.92; H, 5.29%.
tert-Butyl 7-(4-Chlorophenyl)-3-methyl-2-(4-nitrophen-
yl)-5-oxo-7,8-dihydro-2H-pyrano[3,2-c]pyridine-6(5H)-car-
boxylate (11a): Yield 71%; white solids; mp 87-88 °C (from
ethyl acetate-hexane); IR (KBr): ¯ = 3072, 2982, 2935, 1708,
1606, 1525, 1492, 1348, 1286, 1151, 1012 cm¹1; 1H NMR (600
MHz, CDCl3): ¤ 8.30-8.17 (m, 1H), 8.06-7.96 (m, 1H), 7.58-
7.48 (m, 1H), 7.33-7.27 (m, 1H), 7.22-7.17 (m, 1H), 7.17-7.11
(m, 2H), 7.02 (d, J = 8.3 Hz, 1H), 6.46 (d, J = 1.7 Hz, 1H),
5.63 (d, J = 20.0 Hz, 1H), 5.55 (dd, J = 24.5, 5.1 Hz, 1H),
3.25 (dd, J = 17.1, 6.2 Hz) and 3.05 (dd, J = 18.0, 6.7 Hz)
(total 1H), 2.56 (d, J = 17.0 Hz) and 2.48 (dd, J = 17.1, 2.1 Hz)
(total 1H), 1.61 (d, J = 12.6 Hz, 3H), 1.50 (d, J = 1.3 Hz,
9H); 13C NMR (151 MHz, CDCl3): ¤ 163.1, 162.6, 159.5,
144.4, 138.8, 133.5, 128.8 (two peaks), 128.5, 128.0, 126.9
(two peaks), 124.1 (three peaks), 123.8, 114.6, 114.0, 83.4
(two peaks), 81.3, 81.0, 54.5, 54.3, 33.5, 33.3, 28.2, 28.0
(two peaks), 19.2 (two peaks). Anal. Calcd for C26H25ClN2O6:
C, 62.84; H, 5.07; N, 5.64%. Found: C, 62.60; H, 4.92; N,
5.59%.
tert-Butyl 7-(4-Chlorophenyl)-2-(4-methoxyphenyl)-3-
methyl-5-oxo-7,8-dihydro-2H-pyrano[3,2-c]pyridine-6(5H)-
carboxylate (11b): Yield 69%; white solids; mp 83-84 °C
(from ethyl acetate-hexane); IR (KBr): ¯ = 3072, 2978, 2839,
1712, 1681, 1512, 1398, 1298, 1138 cm¹1; 1H NMR (600 MHz,
CDCl3): ¤ 7.32-7.24 (m, 2H), 7.21-7.13 (m, 2H), 7.04 (d,
J = 8.2 Hz, 1H), 6.95-6.86 (m, 2H), 6.72-6.67 (m, 1H), 6.39
(s, 1H), 5.58-5.47 (m, 2H), 3.81 (d, J = 6.6 Hz, 3H), 3.20 (dd,
J = 17.1, 6.2 Hz) and 3.03 (dd, J = 18.0, 6.7 Hz) (total 1H),
2.56-2.49 (m) and 2.46 (dd, J = 17.1, 2.1 Hz) (total 1H), 1.57
(d, J = 10.3 Hz, 3H), 1.51 (d, J = 3.1 Hz, 9H); 13C NMR (151
MHz, CDCl3): ¤ 159.3, 153.0 (two peaks), 130.4, 130.0, 129.4,
128.7 (two peaks), 128.5, 127.1 (two peaks), 125.5, 114.1,
113.9, 113.5, 112.8, 83.1 (two peaks), 82.6, 82.3, 55.3 (two
peaks), 54.4 (two peaks), 33.5, 33.2, 28.0, 19.3 (two peaks).
Anal. Calcd for C27H28ClNO5: C, 67.28; H, 5.86; N, 2.91%.
Found: C, 67.20; H, 5.53; N, 2.84%.
3-Methyl-2-(4-nitrophenyl)-7,7-diphenyl-7,8-dihydro-
pyrano[4,3-b]pyran-5(2H)-one (7a): Yield 73%; yellowish
solids; mp 104-105 °C (from ethyl acetate-hexane); IR (KBr):
¯ = 3059, 2912, 2856, 1708, 1633, 1523, 1398, 1346, 1228,
1
1166 cm¹1; H NMR (400 MHz, CDCl3): ¤ 8.17-8.10 (m, 2H),
7.43-7.13 (m, 12H), 6.32 (d, J = 0.6 Hz, 1H), 5.74 (s, 1H),
3.31 (d, J = 17.4 Hz, 1H), 3.16 (d, J = 17.4 Hz, 1H), 1.58
(d, J = 0.6 Hz, 3H); 13C NMR (101 MHz, CDCl3): ¤ 164.1,
161.6, 148.3, 144.3, 142.8, 142.2, 128.8-128.3 (multiple
peaks), 127.9 (two peaks), 125.4 (two peaks), 124.0 (two
peaks), 114.1, 102.4, 84.1, 81.6, 37.1, 19.0. Anal. Calcd for
C27H21NO5: C, 73.79; H, 4.82; N, 3.19%. Found: C, 73.71; H,
4.87; N, 3.14%.
2-(4-Methoxyphenyl)-3-methyl-7,7-diphenyl-7,8-dihydro-
pyrano[4,3-b]pyran-5(2H)-one (7b): Yield 68%; greenish
solids; mp 128-129 °C (from ethyl acetate-hexane); IR (KBr):
¯ = 3059, 2931, 2835, 1693, 1631, 1512, 1302, 1255, 1170
cm¹1; 1H NMR (600 MHz, CDCl3): ¤ 7.36 (dd, J = 8.3, 1.0 Hz,
2H), 7.34-7.13 (m, 10H), 6.85-6.81 (m, 2H), 6.23 (s, 1H), 5.64
(s, 1H), 3.84 (s, 3H), 3.23 (d, J = 17.6 Hz, 1H), 3.12 (d, J =
17.6 Hz, 1H), 1.56 (d, J = 7.8 Hz, 3H); 13C NMR (151 MHz,
CDCl3): ¤ 164.5, 161.9, 160.2, 143.4, 142.5, 130.1, 129.3,
128.4 (two peaks), 127.6 (two peaks), 125.8, 125.4, 125.1,
114.1, 113.2, 102.0, 83.9, 82.9, 55.3, 37.3, 19.2. Anal. Calcd
for C28H24O4: C, 79.22; H, 5.70%. Found: C, 79.23; H, 5.73%.
2-(4-Chlorophenyl)-3-methyl-7,7-diphenyl-7,8-dihydro-
pyrano[4,3-b]pyran-5(2H)-one (7c):
Yield 75%; white
solids; mp 70-71 °C (from ethyl acetate-hexane); IR (KBr):
¯ = 3061, 2924, 2854, 1708, 1633, 1448, 1398, 1230, 1166
cm¹1; 1H NMR (600 MHz, CDCl3): ¤ 7.36 (dd, J = 5.6, 3.7 Hz,
3H), 7.33-7.23 (m, 5H), 7.23-7.16 (m, 4H), 7.13 (d, J = 8.4
Hz, 2H), 6.27 (s, 1H), 5.64 (s, 1H), 3.25 (d, J = 17.5 Hz, 1H),
3.13 (d, J = 17.5 Hz, 1H), 1.57 (d, J = 9.8 Hz, 3H); 13C NMR
(151 MHz, CDCl3): ¤ 164.3, 161.7, 143.2, 142.3, 136.2, 135.2,
129.2, 128.4 (two peaks), 128.3, 127.7 (two peaks), 125.7,
125.4 (two peaks), 124.5, 113.7, 82.2, 37.2, 19.1. Anal. Calcd
tert-Butyl 7-(4-Chlorophenyl)-3-methyl-5-oxo-2-phenyl-
7,8-dihydro-2H-pyrano[3,2-c]pyridine-6(5H)-carboxylate
(11c): Yield 62%; white solids; mp 80-81 °C (from ethyl
acetate-hexane); IR (KBr): ¯ = 3063, 2980, 2931, 1712, 1629,
¹1
1492, 1396, 1296, 1138, 1089 cm
;
1H NMR (600 MHz,
CDCl3): ¤ 7.42-7.34 (m, 3H), 7.32-7.24 (m, 2H), 7.22-7.12
(m, 2H), 7.06-6.97 (m, 2H), 6.40 (s) and 6.26 (d, J = 15.9 Hz)
(total 1H), 5.59-5.53 (m) and 5.51 (d, J = 5.8 Hz) (total 2H),
3.21 (dd, J = 17.2, 6.3 Hz) and 3.05 (dd, J = 17.9, 6.7 Hz)

M. I. Hossain et al.
Bull. Chem. Soc. Jpn. Vol. 86, No. 7 (2013)
879
(total 1H), 2.50 (ddd, J = 36.8, 17.6, 1.7 Hz, 1H), 1.57 (d,
J = 8.4 Hz, 3H), 1.51 (d, J = 4.0 Hz, 9H); 13C NMR (151 MHz,
CDCl3): ¤ 163.4, 162.8, 159.9, 159.4, 128.3, 127.8 (two peaks),
127.25-127.01 (multiple peaks), 126.7, 125.3, 125.1, 113.5,
112.9, 105.6, 105.3, 83.1 (two peaks), 82.9, 82.6, 60.3, 54.4
(two peaks). Anal. Calcd for C26H26ClNO4: C, 69.10; H, 5.80;
N, 3.10%. Found: C, 68.90; H, 5.71; N, 2.98%.
References
Comprehensive Heterocyclic Chemistry III, ed. by A. R.
Katritzky, C. A. Ramsden, E. F. V. Scriven, R. J. K. Taylor,
Elsevier, Oxford, 2008, Vol. 7.
1
2
For reviews, see: a) I. Larrosa, P. Romea, F. Urpí,
Tetrahedron 2008, 64, 2683. b) Y. Tang, J. Oppenheimer, Z.
Song, L. You, X. Zhang, R. P. Hsung, Tetrahedron 2006, 62, 10785.
3
For a review, see: R. P. Hsung, A. V. Kurdyumov, N.
Sydorenko, Eur. J. Org. Chem. 2005, 23.
Reviews on iminium activation: a) P. Melchiorre, M.
tert-Butyl 7-(4-Chlorophenyl)-2,3-dimethyl-5-oxo-7,8-di-
hydro-2H-pyrano[3,2-c]pyridine-6(5H)-carboxylate (11d):
Yield 72%; white solids; mp 140-141 °C (from ethyl acetate-
hexane); IR (KBr): ¯ = 3028, 2980, 2929, 1712, 1674, 1494,
4
Marigo, A. Carlone, G. Bartoli, Angew. Chem., Int. Ed. 2008, 47,
6138. b) S. Mukherjee, J. W. Yang, S. Hoffmann, B. List, Chem.
Rev. 2007, 107, 5471. c) G. Lelais, D. W. C. MacMillan, in
Enantioselective Organocatalysis, ed. by P. I. Dalko, Wiley-VCH,
Weinheim, 2007, Chap. 3, p. 95. doi:10.1002/9783527610945.
ch3. d) A. Erkkilä, I. Majander, P. M. Pihko, Chem. Rev. 2007,
107, 5416.
1
1413, 1300, 1139 cm¹1; H NMR (600 MHz, CDCl3): ¤ 7.30-
7.24 (m, 2H), 7.15 (t, J = 9.1 Hz, 2H), 6.17 (s) and 6.10 (s)
(total 1H), 5.55 (d, J = 6.4 Hz, 1H), 4.80-4.71 (m, 1H), 3.25-
3.14 (m, 1H), 2.60-2.49 (m, 1H), 1.69 (s, 3H), 1.49 (d, J =
11.5 Hz, 9H), 1.30 (d, J = 6.5 Hz) and 1.14 (d, J = 6.5 Hz)
(total 3H); 13C NMR (151 MHz, CDCl3): ¤ 163.4, 163.0, 160.0,
159.5, 153.1, 139.0 (two peaks), 133.2, 128.6 (two peaks),
127.6, 127.1 (two peaks), 112.6, 112.2, 106.0, 83.0 (two
peaks), 54.5, 54.3, 33.4, 33.2, 28.0 (two peaks), 19.1 (two
peaks), 18.9, 18.7. Anal. Calcd for C21H24ClNO4: C, 64.69; H,
6.20; N, 3.59%. Found: C, 64.70; H, 6.20; N, 3.55%.
3,6-Dimethyl-2-(4-nitrophenyl)-2H-pyrano[3,2-c]quino-
lin-5(6H)-one (13a): Yield 95%; greenish solids; mp 170-
171 °C (from ethyl acetate-hexane); IR (KBr): ¯ = 3080, 2910,
2856, 1666, 1633, 1521, 1396, 1346, 1182 cm¹1; 1H NMR (600
MHz, CDCl3): ¤ 8.23-8.15 (m, 2H), 7.80 (dd, J = 8.0, 1.5 Hz,
1H), 7.67-7.58 (m, 2H), 7.51 (ddd, J = 8.6, 7.2, 1.5 Hz, 1H),
7.32-7.24 (m, 1H), 7.19-7.13 (m, 1H), 6.90-6.85 (m, 1H), 5.95
(s, 1H), 3.69 (s, 3H), 1.82 (d, J = 0.5 Hz, 3H); 13C NMR (151
MHz, CDCl3): ¤ 160.5, 152.7, 148.2, 145.0, 139.0, 130.9,
128.5, 127.3, 124.0, 122.6, 121.9, 116.2, 115.2, 114.1, 106.5,
80.2, 29.4, 19.7. Anal. Calcd for C20H16N2O4: C, 68.96; H,
4.63; N, 8.04%. Found: C, 69.05; H, 4.63; N, 8.04%.
5
a) L.-F. Tietze, G. V. Kiedrowski, B. Berger, Synthesis
1982, 683. b) L. F. Tietze, C. Bärtels, Liebigs Ann. Chem. 1991,
155. c) H. Hu, T. J. Harrison, P. D. Wilson, J. Org. Chem. 2004,
69, 3782.
6
a) G. Cravotto, G. M. Nano, S. Tagliapietra, Synthesis
2001, 49. b) G. Appendino, G. Cravotto, S. Tagliapietra, G. M.
Nano, G. Palmisano, Helv. Chim. Acta 1990, 73, 1865.
7
R. P. Hsung, H. C. Shen, C. J. Douglas, C. D. Morgan, S. J.
Degen, L. J. Yao, J. Org. Chem. 1999, 64, 690.
a) M. J. Riveira, M. P. Mischne, Synth. Commun. 2013, 43,
208. b) Z. Zhou, Y. Sun, Synth. Commun. 2011, 41, 3162.
Y.-R. Lee, D.-H. Kim, J.-J. Shim, S. K. Kim, J.-H. Park,
8
9
J.-S. Cha, C.-S. Lee, Bull. Korean Chem. Soc. 2002, 23, 998.
10 Lewis acid: A. V. Kurdyumov, N. Lin, R. P. Hsung, G. C.
Gullickson, K. P. Cole, N. Sydorenko, J. J. Swidorski, Org. Lett.
2006, 8, 191.
11 E.-J. Jung, Y.-R. Lee, H.-J. Lee, Bull. Korean Chem. Soc.
2009, 30, 2833.
12 W. Peng, T. Hirabaru, H. Kawafuchi, T. Inokuchi, Eur. J.
Org. Chem. 2011, 5469.
13 a) C. M. Moorhoff, Synthesis 1997, 685. b) G. V. Kryshtal,
V. V. Kulganek, V. F. Kucherov, L. A. Yanovskaya, Synthesis 1979,
107.
3,6-Dimethyl-2-phenyl-2H-pyrano[3,2-c]quinolin-5(6H)-
one (13b): Yield 92%; white solids; mp 162-163 °C (from
ethyl acetate-hexane); IR (KBr): ¯ = 3074, 2972, 2928, 1654,
¹1
1633, 1587, 1452, 1398, 1111 cm
;
1H NMR (600 MHz,
CDCl3): ¤ 7.83 (dd, J = 8.0, 1.4 Hz, 1H), 7.51-7.42 (m, 3H),
7.36-7.31 (m, 3H), 7.29-7.25 (m, 1H), 7.17-7.11 (m, 1H),
6.85-6.79 (m, 1H), 5.88 (s, 1H), 3.69 (s, 3H), 1.79 (s, 3H);
13C NMR (151 MHz, CDCl3): ¤ 160.8, 153.0, 138.9, 138.3,
130.4, 128.9, 128.7 (two peaks), 127.7, 122.8, 121.6, 115.6,
115.2, 113.9, 106.5, 81.7, 29.3, 19.8. Anal. Calcd for
C20H17NO2: C, 79.19; H, 5.65; N, 4.62%. Found: C, 79.13;
H, 4.48; N, 4.57%.
14 a) A. K. Bhattacharya, R. P. Sharma, Heterocycles 1999,
51, 1681. b) C. Liu, Y. Wang, F. Ouyang, H. Ye, G. Li, Huaxue
Jinzhan 1999, 11, 41.
15 a) P. de A. Amaral, J. Petrignet, N. Gouault, T. Agustini,
F. Lohézic-Ledévéhat, A. Cariou, R. Grée, V. L. Eifler-Lima, M.
David, J. Braz. Chem. Soc. 2009, 20, 1687. b) B. Andersh, J.
Gereg, M. Amanuel, C. Stanley, Synth. Commun. 2008, 38, 482.
c) P. A. Amaral, N. Gouault, M. L. Roch, V. L. Eifler-Lima, M.
David, Tetrahedron Lett. 2008, 49, 6607. d) B. D. Tait, S. Hagen, J.
Domagala, E. L. Ellsworth, C. Gajda, H. W. Hamilton, J. V. N. V.
Prasad, D. Ferguson, N. Graham, D. Hupe, C. Nouhan, P. J.
Tummino, C. Humblet, E. A. Lunney, A. Pavlovsky, J. Rubin, S. J.
Gracheck, E. T. Baldwin, T. N. Bhat, J. W. Erickson, S. V. Gulnik,
B. Liu, J. Med. Chem. 1997, 40, 3781.
We are grateful to Okayama University for its support and to
the Advanced Science Research Center for the NMR experi-
ments, EA by Ms. M. Kosaka and Mr. M. Kobayashi, and X-
ray analyses by Dr. H. Ota. This study was partially supported
by the Adaptable and Seamless Technology Transfer Program
of JST.
16 a) N. S. Suryawanshi, P. Jain, M. Singhal, J. Chemtracks
2011, 13, 127. b) C. Su, Z.-C. Chen, Q.-G. Zheng, Synthesis 2003,
555.
Supporting Information
17 a) M. J. Ashton, S. J. Hills, C. G. Newton, J. B. Taylor,
S. C. D. Tondu, Heterocycles 1989, 28, 1015. b) E. Vanotti, B.
Forte, K. Martina, M. Menichincher, A. Cirla, P. Orsini, EU Patent
EP 1 963 319 B1, 2012.
1
Spectral data including H NMR and 13C NMR spectra of
3a-3s, 7a-7d, 11a-11d, 13a, and 13b are provided. This mate-
rial is available free of charge on the Web at: http://www.csj.jp/
journals/bcsj/.